Incontinence therapy

ABSTRACT

Urinary incontinence such as stress incontinence, is alleviated in a mammal, in particular a human being, especially a woman, by correcting the internal urethral orifice and the urethra with an elastic form stable material. Such a material preferably a curable elastomer-precursor composition is injected in the body tissue surrounding the urethra, thereby correcting internal urethral orifice and the urethra substantially to its original shape, allowing the sphincter to act in a controllable way.

TECHNICAL FIELD

The present invention relates to a method of treating urinaryincontinence, in particular stress incontinence, in mammals, inparticular human beings, especially females. This invention also relatesto a composition suitable for use in such a method, its preparation anduse.

BACKGROUND ART

Stress incontinence is a phenomenon which frequently occurs in humanbeings, in particular elder human beings. This uncontrolled andunvoluntary leakage of urine is related to physical activities whichstrain the abdominal muscles such as coughing, sneezing, lifting ofheavy objects, climbing of stairs, etc. The sphincter cannotsufficiently contract in order to resist the increased tension in theabdomen including enlarged tension on the bladder, and undesirable lossof urine is the result. This condition is more common in the femalepopulation and is usually associated with weakened pelvic floor musclesrelated to multiple births and menopause. Also a deficiency of certainfemale hormones (estrogens) during the menopause can effect thesphincter of the bladder. In the male population, it may be related tocertain surgical procedures. Obesity, e.g. derived from diabetusmellitus is another possible cause. Although stress incontinence isusually a periodically occuring phenomenon, the leaking can worsen andbecome constant.

In order to treat this kind of incontinence various therapies exist.Examples thereof comprise physiotherapy in order to strengthen thepelvic floor muscles by exercise and training. Therapy with hormones isanother example. Lowering of the uterus can be counteracted by apessarium. However, if these therapies do not have the desired effect,surgery is a further option. One of the surgical options is theapplication of a tension free vaginal tape. This tape is positioned at aposition under the urethra, and supports this during activities such ascoughing, laughing and lifting.

Another surgical method comprises so-called colposuspensions, e.g.according to Burch, wherein the mouth of the urethra is raised andsuspended to the inner side of the pubic bone. Other physicians are alsousing injections of collagen or silicone particles in the wall of theurethra to bulk up the urethra and try to limit leakage that way.Thereby the cross dimension of the urethra is reduced, as a result ofwhich the urine can flow less easily from the bladder. However, collagenis resorbable by the body, as a result of which it is apt to reduce itsaction. Particles, such as the silicone particles are apt to migrate inthe body. Thus their position is not maintained, as a result of whichthe effect is not ensured, and even reduced in time.

Although some of the treatments mentioned above have shown to besuccesfull at least initially at the start of the treatment, the successrate is not easy to predict. Moreover, as the general bodily conditionof a patient suffering from incontinence may change over the years, theeffectiveness of a certain therapy may become less. In particularinjection of particulate material has not been attractive to patientsand therefore has not been accepted broadly. Moreover, it is known thatthe success rate of this kind of treatment is far less compared to theother techniques mentioned above.

As a consequence, there is still a continued need for alternativemethods in addition to the existing methods of counteracting stressincontinence, in particular methods which are easy to perform.

There is also a continued need for materials which are effective incounteracting stress incontinence when applied to a mammal, such as ahuman being.

SUMMARY OF THE INVENTION

In accordance with the present invention, there is provided a method oftreating incontinence in a mammal including human beings, in particularwomen, comprising a step of correcting the shape of the internalurethral orifice and the urethra with an elastic form stable material,preferably comprising a curable elastomer-precursor composition.According to the invention, human beings in particular elder womensuffering from stress incontinence, are treated by remodelling of theinternal urethral orifice (the transition from the bladder to theurethra) and urethra into a shape wherein the effect of the forceapplied by the sphincter to the urethra and bladder in order to keep itclosed, is enhanced. This favourabe shape of the urethra is permanentlyinduced by the form stable material. After curing this non-resorbablematerial is a solid mass compared to particulate material and cannotmigrate through the body, but holds its initial position where it isapplied. Simultaneously the form stable material itself is flexibleenough to adapt to body movements, so that a patient treated accordingto the invention does not experience any discomfort.

This elastic form stable material preferably comprises anelastomer-precursor composition which is cured in situ. That is to say,the elastomer precursor is prepared in advance and then applied to theappropriate positions by suitable equipment. At these positions thecuring of the material thus applied is completed. Surprisingly, it wasfound that a form stable material made from an elastomeric compositionnot only is more convenient to the patient treated, but also allows toremodel the internal urethral orifice and the urethra into its originalshape wherein forces exerted by the sphincter are sufficient to preventleakage of urine.

The invention also relates to a method of preparing a composition forthe treatment of incontinence in a mammal, in particular human beings,especially women, which composition comprises an elastic form stablematerial, preferably a curable elastomer-precursor-composition. Saidtreatment of incontinence is the shape correction of the urethra andinternal urethral orifice.

A further aspect of the invention concerns the use of elastic formstable material, preferably a curable elastomer-precursor composition,in the treatment of urinary incontinence in mammals, in particular humanbeings, especially women.

THE DRAWINGS

For a fuller understanding of the nature and objects of the invention,reference should be had to the following detailed description taken inconnection with the accompanying drawings, in which:

FIG. 1 is a diagramatic view showing a normal bladder and urethra, withthe bladder filled with urine;

FIG. 2 is a diagramatic view showing a bladder and urethra, with thebladder filled with urine, in an individual suffering from incontinence;and

FIG. 3 is a diagramatic view showing the bladder and urethra of FIG. 2,after treatment in accordance with the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

According to a preferred embodiment, the correction step comprisesinjecting a curable elastomer-precursor composition in the body tissuesurrounding the urethra. Contrary to the collagen and silicone therapiesaccording to the state of the art, wherein the composition is applied inthe wall of the urethra, the correcting composition according to theinvention is injected through the wall of the urethra in the tissuedirectly adjacent to the urethra. Preferably the composition is injectedin at least three periheral positions in order to allow said correction.More preferably several injections are carried out in such a way thatthe cured composition completely surrounds the urethra as an annularsupport.

Commercially available medical grade silicone elastomers are preferredmaterials for use as polymer precursor in the remodelling composition. Amore preferred material is poly(dimethyl siloxane) such ashydroxyl-end-blocked poly(dimethyl siloxane). Such silicone elastomersof medical grade as pourable, two-component silicone are available frome.g. NuSil Technology. These silicone elastomers are fast curingmaterials. For these types of elastomers propyl orthosilicate is auseful cross-linking agent. Fillers and diluents (medicinal fluids suchas known under the trade name Dimeticonum) in order to reduce viscositymay be added as needed. An initiator like tin (II) octoate initiates thepolymerisation reaction with splitting of propanol. The reactionproceeds without the generation of sensible heat. Silphenylene polymercan be used in a similar way. In order to be able to trace by X-raymonitoring the position of the cured applied composition, in a preferredembodiment the composition comprises a radiopaque material, such assilver powder, barium sulfate or bismuth trioxide.

Here it is noted that a composition as explained above is known per seas a material suitable for the non-surgical, reversible sterilization offemales. In this known sterilization method the composition is injectedin the oviduct portion adjacent the uterus, where it forms in situ ablock or plug in the oviduct, thereby preventing the passage of ovumfrom the ovaries to the uterus and sperm from entering the oviduct andthus conception. See e.g. U.S. Pat. No. 4,245,623.

A preferred composition for use in the method according to the inventioncomprises about 60-75% by weight poly(dimethyl siloxane), about 2-5%cross-linking agent, a diluent in the range of 10-20% and about 10-20%radiopaque powder. An even more preferred composition comprises about 68wt. % poly(dimethyl siloxane), about 4% cross-linking agent, about 13%dimeticonum and about 16% silver powder

In the method according to the invention the composition isadvantageously prepared in advance in a mixing-dispensing device. Such adevice, wherein the function of mixing the components is combined withthe function of dispensing the thus prepared mixture is known per se,e.g. from the above US patent, the content of which is incorporated inits entirety by reference.

As already indicated above, the invention also relates to a method ofpreparing a composition for the treatment of incontinence, in particularstress incontinence, in mammals in particular human beings, especiallywomen, which composition comprises an elastic form stable composition,preferably a curable elastomer-precursor composition. Theabove-mentioned preferred features of the treatment method according tothe invention are similarly applicable to the preparation methodaccording to the invention.

Advantageously the correcting composition is packaged as a kit of parts,comprising at least a first container filled with an elastomer precursorand optionally a diluent, and a second container filled with across-linking agent for this elastomer precursor. More preferably, thecomposition is packaged in a mixing-dispensing device, comprising suchcontainers and a temporarily seal between the containers, wherein one ofthese containers is provided with a stirrer which can be operatedmanually or powered by an external source. An example of such a deviceis also known from the above-mentioned US patent.

Devices of this type can be used for injecting the thus preparedprecursor composition by connecting a suitable flexible tube to thecontainer acting as a mixing chamber and providing an appropriate needleat the other end of the tube.

In the invention a flowable composition is prepared from the variouscomponents, preferably in a combined mixing-dispensing device asexplained above, and then immediately used. The patient is prepared forthe treatment according to standard medical procedures. A catheter isbrought into the urethra until the injection needle reaches the bladder,e.g. indicated by the presence of a droplet of urine, and then retractedover a predetermined distance, e.g. in the range of 1-2 cm. At theposition thus reached the wall of the urethra is punctured by theinjection needle, and the composition is forced from the respectivecontainer via a suitable flexible tube to the needle and depositeddirectly adjacent this wall in the respective tissue. In order to moreaccurately position the deposit of the composition, preferably theneedle is not open at the tip but has one or more exits at the side facedirectly adjacent to the tip. Use of this modified needle allows toposition the composition more easily adjacent the urethra wall.Thereafter the needle is retracted and the composition is allowed tocure in situ. As already mentioned preferably the composition is appliedat multiple locations surrounding the urethra. In view thereof the aboveactions can be repeated as needed.

By referring to FIGS. 1-3, along with the following detailed discussion,both the use and efficacy of the present invention can best beunderstood. As shown in FIG. 1, an individual, who does not suffer fromincontinence, is able to completely retain urine 22 in bladder 21 by useof sphincter muscles 23. In such individuals, urine 22 is forced out ofbladder 21 through urethra 24 by controlling sphincter muscles 23 andbladder muscles 25.

As discussed above, many individuals suffer from incontinence due to theinability of their sphincter muscles 23 to operate in the normal manner.As a result, as depicted in FIG. 2, urine 22 is able to leak throughurethra 24 due to the inability of sphincter muscles 23 to maintainurethra 24 completely closed, as desired.

In order to eliminate this leakage problem, which plagues numerousindividuals, the treatment provided by the present invention has beendeveloped. As detailed above, by injecting a curable elastomer-precursorcomposition 28 into the tissue surrounding the urethra, in the areaadjacent the bladder, normal control of the sphincter muscles isreestablished.

As shown in FIG. 3, and fully detailed above, the desired curableelastomer-precursor composition 28 is injected into the tissuesurrounding urethra 24 in a plurality of separate and independentlocations. In the preferred method, at least three locations areemployed, with the injection site locations defining a substantiallyannular shape about urethra 24. By employing this method, it has beenfound that substantially normal control over sphincter muscles 23 arereestablished, and the incontinence problems that had previously existedare substantially eliminated.

Although the curable elastomer-precursor composition employed can bewidely varied and the precise number and location of injection sitesabout urethra 24 may also be widely varied, all such alterations and/orvariations are encompassed within the scope of the present invention.Although the preferred composition and injection site locations aredetailed herein, the present invention is intended to encompass allvariations coming within the overall disclosure of this invention.

It will thus be seen that the objects set forth above, among those madeapparent from the preceding description, are efficiently attained and,since certain changes may be made in carrying out the above methodwithout departing from the scope of the invention, it is intended thatall matter contained in the above description, or shown in theaccompanying drawings, shall be interpreted as illustrative and not in alimiting sense.

It is also to be understood that the following claims are intended tocover all of the generic and specific features of the invention hereindescribed, and all statements of the scope of the invention which, as amatter of language, might be said to fall therebetween.

Having described my invention, what I claim as new and desire to secureby Letters Patent is:

1. A method of counteracting incontinence in a mammal, in particularhuman beings, especially women, comprising a step of correcting theshape of the internal urethral orifice and urethra with an elastic formstable material.
 2. The method defined in claim 1, wherein saidcorrection comprises injecting a curable elastomer-precursor compositionin the body tissue surrounding the urethra.
 3. The method defined inclaim 2, wherein said curable elastomer-precursor composition isinjected at least in three positions.
 4. The method defined in claim 3,wherein said curable elastomer-precursor composition is further definedas being injected at three positions which composition peripherallysurrounds the urethra.
 5. The method defined in claim 2, wherein saidcurable elastomer-precursor composition is further defined as beinginjected about the urethra in a substantially annular array.
 6. Themethod method defined in claim 2, wherein said curableelastomer-precursor composition comprises a silicone elastomer.
 7. Themethod defined in claim 6, wherein said silicone elastomer comprisespoly(dimethyl siloxane).
 8. The method defined in claim 2, whereincurable elastomer-precursor composition comprises a silicone elastomer,a cross-linking agent and a diluent.
 9. The method defined in claim 8,wherein said curable elastomer-precursor composition is further definedas comprising bewteen about 60% and 75% by weight based on the weight ofthe entire composition of poly(dimenthyl siloxane), between about 2% and5% by weight based upon the weight of the entire composition of across-linking agent, between about 10% and 20% by weight based upon theweight of the entire composition of a diluent, and between about 10% and20% by weight based upon the weight of the entire composition of aradiopaque powder.
 10. The method defined in claim 2, wherein saidcurable elastomer-precursor composition comprises radiopaque material.11. The method defined in claim 2, wherein said curableelastomer-precursor composition is further defined as comprising atleast two components which are intermixed in advance in a combinedmixing dispensing device and then dispensed when needed.
 12. A methodfor treating incontinence in a mammal, particularly human beings,especially women, comprising the steps of A. forming an elastic formstable material comprising a curable elastomer-precursor composition; B.injecting the elastic, form stable material into the tissue surroundinga urethra directly adjacent a bladder; and C. allowing the form stablematerial to cure in situ.
 13. The method defined in claim 12, whereinthe curable elastomer-precursor composition comprises a siliconeelastomer.
 14. The method defined in claim 13, wherein said siliconeelastomer comprises poly(dimethoxy siloxane).
 15. The method defined inclaim 12, wherein said curable elastomer-precursor silicone elastomer, across-linking agent and a diluent.
 16. The method defined in claim 12,wherein said composition comprises a radiopaque material.
 17. The methoddefined in claim 15, wherein said composition further defined as being akit, comprising a first container filled with said silicone elastomerand said diluent, and a second container with said cross-linking agent.18. The method defined in claim 12, wherein said injection step isfurther defined as being repeated in a plurality of sites peripherallysurrounding the urethra.
 19. The method defined in claim 12, whereinsaid injection step is further defined as being performed using acatheter advanced through the urethra to an injection site rangingbetween about 1 cm and 10 cm prior to the junction of the urethra withthe bladder.